We have applied a new approach for establishing cultures of human plasma cells for producing human monoclonal antbodies. The approach utilizes the cell-transforming (immortalizing) activity of Epstein-Barr virus (EBV). Previously, attempts to establish human myeloma cell lines by EBV infection were unsuccessful because the cells lack EBV receptors. We have demonstrated that transplantation of functional EBV receptors permits infection of any human and animal cell by the virus, including myeloma cells. During the first year of our program, we have established experimental procedures for purifying plasma cells from blood of patients with multiple myeloma. We have implanted the cells with EBV receptors and infected them with the virus. EBV infection of the myeloma cells resulted in the establishment of several plasma cell-containing, EBV genome-positive cell lines. The cell lines, designated MS-1, MS-2, and MS-3, were heterogenous for surface markers, but each of them contain at least 50% of mature plasma cells. The lines of the MS series grow continuously in culture, they are positive for cytoplasmic immunoglobulin, and are clonable in soft agar. In the next year of the project, we plan the following: (1) establish several additional EBV-transformed human myeloma cell lines; (2) evaluate all the established cell lines for surface markers and intracellular immunoglobulin synthesis; (3) clone out the cells to establish monoclonal cultures consisting of nonsecreting plasma cells; and (4) initiate testing the myeloma cell clones for their ability and efficiency to fuse with human lymphocytes. (2)